All atomic nuclei of elements with an odd atomic mass or an odd atomic number possess a nuclear magnetic moment. Nuclear magnetic resonance is a phenomenon exhibited by this select group of atomic nuclei (termed "NMR active" nuclei), and is based upon the interaction of the nucleus with an applied, external magnetic field. The magnetic properties of a nucleus are conveniently discussed in terms of two quantities: the gyromagnetic ratio (.gamma.); and the nuclear spin (I). When an NMR active nucleus is placed in a magnetic field, its nuclear magnetic energy levels are split in to (2I+1) non-degenerate energy levels, which are separated from each other by an energy difference that is directly proportional to the strength of the applied magnetic field. This splitting is called the "Zeeman" splitting and the energy difference is equal to H.sub.0 /2.pi. where is Planck's constant and H.sub.0 is the strength of the applied magnetic field. The frequency corresponding to the energy of the Zeeman splitting (.omega..sub.0 =.gamma.H.sub.0) is called the "Larmor frequency" and is proportional to the field strength of the magnetic field. Typical NMR active nuclei include .sup.1 H (protons), .sup.31 P, .sup.13 C and .sup.19 F. For these four nuclei I=1/2, and each nucleus has two nuclear magnetic energy levels.
When a bulk sample of material containing NMR active nuclei is placed within a magnetic field called the main static field, the nuclear spins distribute themselves amongst the nuclear magnetic energy levels in accordance with Boltzmann's statistics. This results in a population imbalance among the energy levels and a net nuclear magnetization. It is this net nuclear magnetization that is studied by NMR techniques.
At equilibrium, the net nuclear magnetization of the aforementioned bulk sample is aligned parallel to the external magnetic field and is static (by convention, the direction of the main static field is taken to be the z-axis of a three-axis Cartesian coordinate system). A second magnetic field perpendicular to the main static magnetic field and rotating at, or near, the Larmor frequency can be applied to induce a coherent motion of the net nuclear magnetization. Since, at conventional main static magnetic field strengths, the Larmor frequency is in the megahertz frequency range, this second magnetic field is called a "radio frequency" or RF field.
The effect of the RF field is to shift the nuclear magnetization direction so that it is no longer parallel to the main static field. This shift introduces a net coherent motion of the nuclear magnetization about the main static field direction called a "nutation". In order to conveniently deal with this nutation, a reference frame is used which rotates about the laboratory reference frame z-axis at the Larmor frequency and also has its z-axis parallel to the main static field direction. In this "rotating frame" the net nuclear magnetization, which is rotating in the stationary "laboratory" reference frame, is now static.
Consequently, the effect of the RF field is to rotate the now static nuclear magnetization direction at an angle with respect to the main static field direction (z-axis). The new magnetization direction can be broken into a component which is parallel to the main field direction (z-axis direction) and a component which lies in the plane transverse to the main magnetization (x,y plane). Since, in the transverse plane, the x and y directions are relative directions, the pulse designations x and y are used to represent relative phases of the RF field. For example, an RF pulse designated as an "x" pulse has a relative phase shift of 90.degree. with respect to an RF pulse designated as a "y" pulse. Similarly, an RF pulse designated as an "x" pulse has a relative phase shift of 180.degree. relative to an RF pulse designated as a -x pulse, etc. The RF field is typically applied in pulses of varying length and amplitude and, by convention, an RF pulse of sufficient amplitude and length to rotate the nuclear magnetization in the rotating frame through an angle of 90.degree., or .pi./2 radians, and entirely into the x,y plane is called a ".pi./2 pulse".
Because the net nuclear magnetization is rotating with respect to the laboratory frame, the component of the nuclear magnetization that is transverse to the main magnetic field or that lies in the x,y plane rotates about the external magnetic field at the Larmor frequency. This rotation can be detected with a receiver coil that is resonant at the Larmor frequency.
The receiver coil is generally located so that it senses voltage changes along one axis (for example, the x-axis) where the rotating magnetization component appears as an oscillating voltage. Frequently, the "transmitter coil" employed for applying the RF field to the sample and the "receiver coil" employed for detecting the magnetization are one and the same coil.
Although the main static field is applied to the overall material sample, the nuclear magnetic moment in each nucleus within the sample actually experiences an external magnetic field that is changed from the main static field value due to a screening from the surrounding electron cloud. This screening results in a slight shift in the Larmor frequency for that nucleus (called the "chemical shift" since the size and symmetry of the shielding effect is dependent on the chemical composition of the sample).
In a typical NMR experiment, the sample is placed in the main static field and a .pi./2 pulse is applied to shift the net magnetization into the transverse plane (called transverse magnetization). After application of the pulse, the transverse magnetization, or "coherence", begins to precess about the x-axis, or evolve, due to the chemical shifts at a frequency which is proportional to the chemical shift field strength. In the rotating frame, the detector (which is stationary in the laboratory frame) appears to rotate at the Larmor frequency. Consequently, the detector senses an oscillation produced by an apparent magnetization rotation at a frequency which is proportional to the frequency difference between the Larmor frequency and the chemical shift frequency.
In some NMR experiments it is assumed that the RF excitation pulse rotates the entire net magnetization into the transverse plane, even though there are differences between the Larmor frequency and the chemical shift frequency and these differences would normally cause an RF pulse with a narrow frequency response to affect the net magnetization differently. Consequently, rotation of the entire net magnetization into the transverse plane is assured by applying an RF pulse with a large amplitude and a short duration. Such a pulse has a broad frequency response and is called a "hard" RF pulse.
In other NMR experiments, a frequency-selective RF excitation pulse is desired. In these latter experiments, an RF pulse with a narrow frequency response is applied and the RF pulse rotates only the magnetization from spins where the difference between the Larmor frequency and the chemical shift frequency is a specific value. The most straightforward example of a frequency-selective pulse is a long and weak RF pulse, also called a "soft" or selective pulse.
In addition to precessing at the Larmor frequency, in the absence of the applied RF field energy, the nuclear magnetization also undergoes two spontaneous processes: (1) the precessions of various individual nuclear spins which generate the net nuclear magnetization become dephased with respect to each other so that the magnetization within the transverse plane loses phase coherence (so-called "spin-spin relaxation") with an associated relaxation time, T.sub.2 and (2) the individual nuclear spins return to their equilibrium population of the nuclear magnetic energy levels (so-called "spin-lattice relaxation") with an associated relaxation time, T.sub.1, The decaying oscillating signal is called a free induction decay (FID).
Further, although many NMR experiments are designed such that the spin dynamics are uniform through the sample, there are cases where it is advantageous to impose a spatial heterogeneity across the sample. Some examples of these latter cases include imaging experiments, diffusion experiments, coherence transfer experiments (where the heterogeneity may be used as a means of allowing a variation in coherence pathways), and multiple-quantum filtering experiments. All of these experiments can be performed with a spatial heterogeneity created by applying a spatially-varying magnetic field to the sample. Some common examples of such a spatially-varying field include B.sub.0 and B.sub.1 magnetic field gradients which are gradients along the direction of the main static field and in the plane transverse to the main static field direction, respectively.
It is often necessary to obtain NMR spectra from compounds that are dissolved in a solvent. If this solvent generates a strong NMR signal and the concentration of the dissolved compounds is low, then the strong solvent NMR signal may obscure or complicate the observation of the compound resonances. In particular, the obscuring of biological compound signals by water resonance signals is a very pronounced problem in proton NMR of biological systems where the water resonance signals may be 1000 to 10,000 times larger than the biological compound signals of interest. At first glance, it may appear relatively easy to remove the solvent NMR signal, which generally has a known frequency and shape, from the compound NMR signal. However, practically, such is not the case. One reason for this is that the solvent NMR signal may be so strong that it saturates either the analog receiver or the analog-to-digital converter, both of which are normally used to receive and process the overall NMR signal. This saturation introduces artifacts into the NMR signal that, in turn, cannot be easily removed and produce a useless NMR spectrum.
One prior art method for avoiding saturation of the NMR receiver components is to attenuate the overall NMR signal. The attenuation prevents the strong solvent signals from reaching the upper limits of receiver system response, but has the effect of increasing the lower detection limit of the receiver system. Consequently, small compound resonances of interest often fall under the detection limit and are not detected.
Other prior art methods for avoiding receiver system saturation involve suppressing the strong solvent NMR signals before a measurement is taken. In this manner, the small resonances can be detected without risking saturation. There are a large number of existing known techniques which are described in detail in an article entitled "Solvent Signal Suppression in NMR", M. Gueron, P. Plateau and M. Decorps, Progress in Nuclear Magnetic Resonance Spectroscopy, vol. 23, pages 135-209. These prior art techniques include presaturation, diffusion-based techniques, jump-return techniques and binomial pulse sequences.
Despite the large number of prior art solvent suppression techniques, many common problems still exist. For example, presaturation and diffusion-based techniques prevent the observation of exchangeable protons, while methods which rely on jump-return or on binomial pulse sequences lead to signals with frequency dependent phases and/or amplitude variations over the spectra. Further, the latter methods are often accompanied by a baseline distortion.
In experiments where gradients can be used, one prior art approach to overcoming some of the problems with prior art solvent suppression techniques uses B.sub.0 gradients in combination with selective excitation pulses and is described in detailed in a paper entitled "Gradient Tailored Excitation for Single-Quantum NMR Spectroscopy of H.sub.2 O Solutions", M. Piotto, V. Saudek and V. Sklenar, Journal of Biomolecular Nuclear Magnetic Resonance, vol. 2, page 661. As described in this paper, good solvent signal suppression can be achieved with a gradient spin echo sequence which includes both a selective inversion pulse which inverts the solvent resonance and a hard inversion pulse which inverts all resonances. In particular, the selective inversion pulse is split into two selective pulses, which are arranged to sandwich a hard .pi. inversion pulse of opposite phase. When this pulse sequence is applied, the solvent resonance will experience no net rotation and will be dephased, while the solute resonances experience a .pi. rotation, and will be refocussed by the second gradient pulse.
Although each of the solvent suppression techniques discussed above has advantages, all of the techniques also have disadvantages. For example, in addition to the aforementioned problems encountered with prior art solvent suppression techniques, the occurrence of radiation damping is also known to significantly reduce the performance of known solvent suppression techniques. Techniques involving B.sub.0 gradients in addition suffer from artifacts caused by the use of B.sub.0 gradients, such as eddy currents, disturbance of the magnetic field locking system and the need to allow for long delays in the NMR experiment to switch the B.sub.0 gradients on and off. Also, during the time required for the application of the B.sub.0 gradients, the spin magnetization loses phase coherence due to spin-spin relaxation, which loss in phase coherence results in a loss of signal intensity.
Accordingly, it is an object of the present invention to provide a solvent suppression technique that is insensitive to the aforementioned problems encountered with existing techniques.
It is another object of the present invention to provide a solvent suppression technique which can be used in experiments that require a gradient field.